Causative Role of Anoxic Environment in Bacterial Regulation of Human Intestinal Function

Bacterial Influence on Pharmacokinetics of Tacrolimus and Sulfasalazine through Regulation of Host Metabolism

“…[34][35][36] Based on the experimental data from Wang et al and the model presented in this paper, we posit that various combinations of bacteria in both probiotic therapy and natural butyrate production may impact the pharmacokinetics of transporter-dependent oral drugs. [30] There is literature evidence supporting this claim. ECN increases amiodarone's bioavailability while the drug is metabolized by several CYP enzymes, except CYP3A4.…”

“…Wang et al have since conducted experiments showing how two common gut bacterial strains (facultative anaerobe E. coli Nissle 1917 (ECN) and obligate anaerobe Bifidobacterium adolescentis (BIF)) impact the indirect expression of transporters and metabolic enzymes in human colon cells under conditions that mimic the intestinal epithelium-bacterial interface. [30] The results indicate that the expressions of ABCC2, ABCG2, and SLCO2B1 were significantly reduced by both ECN and BID. ABCC2, ABCG2, and SLCO2B1 are genes that lead to the translation of drug transporters multidrug resistance protein 2 (MRP2), breast cancer resistance protein (BCRP), and organic anion transporting poly peptide 2B1 (OATP2B1), all of which play key roles in the intestinal absorption of TAC and/or SASP.…”

“…[40][41][42] Several groups have co-cultured intestinal cells with bacteria to investigate the impact of gut microbes on physiology, disease, and drug metabolism. [30,[43][44][45][46][47][48][49] Lee et al and Xiang et al summarize the benefits of the approach regarding the representation of drug pharmacokinetics in the intestinal environment. [40,41] One of the challenges in modeling the intestinal environment is that the epithelial cells are aerobic whereas the gut bacteria are primarily obligate anaerobic.…”

“…This was addressed in the microfluidic device by forming an aerobic-anaerobic interface that the coculture of the colon epithelial cells with anaerobic gut bacteria. [30,49] Tacrolimus Compartmental Model: The pharmacokinetics of TAC was represented as a two-compartmental model (Figure 1). In previous in silico studies, TAC had been modeled using population pharmacokinetic and compartmental models; however, only Degraeve et al has considered the impact of microbiota on TAC metabolism.…”

“…The model term, M(t), includes an ordinary differential equation (ODE) solver from scipy to estimate the values of the solved ODEs (Equations 1 and 2 for TAC, Equations 3-5 for SASP) at the same time points as the experimental studies (0,2,4,6,8,10, and 12 h for both models with the addition of 16,20,23,30,36, and 48 h for SASP).…”